CLINUVEL PHARMACEUTICALS LTD (ASX: CUV; XETRA‐DAX: UR9; ADR: CLVLY) is a global biopharmaceutical company focused on developing drugs for the treatment of a range of severe disorders. With its unique expertise in understanding the interaction of light and human skin, the company has identified patient populations with a clinical need for photoprotection and another population with a need for repigmentation. These patient groups range in size from 5,000 to 45 million. CLINUVEL’s lead compound, SCENESSE® (afamelanotide 16mg), a first‐in‐class drug targeting erythropoietic protoporphyria (EPP), has completed Phase II and III trials in the US and Europe, and has been approved by the European Commission for treating adults with EPP.

Based in Melbourne, Australia, CLINUVEL has operations in Europe, the US and Singapore.

Skin care ingredients

Skin care is a multi-billion dollar industry, with the biggest markets in Europe and the United States. There is a huge range of skin care products, including; cleansers, toners, moisturisers, sunscreens, exfoliants and masks. In recent years, formulations containing natural ingredients have seen a rise in popularity as people’s concerns grow over the safety of synthetic ingredients. There has also been a marked increase in both the anti-aging and men’s skin care sectors. The following catalogues the most common ingredients constituting skin care products and describes their function and effectiveness. The article Skin care concepts may be a useful tool for understanding some of the terms used here.

A-Z of Ingredients:

Ammonium lactate - the ammonium salt of lactic acid. Ammonium lactate mainly acts as a humectant in moisturisers and other lotions. It is also sometimes used as a buffering agent to maintain the pH balance of a solution when other ingredients are added.

Avobenzone (butyl methoxydibenzoylmethane/ Parsol 1789/ Eusolex 9020/ Escalol 517) - one of the most widely used organic sunscreen active agents, avobenzene is one of the few filters which absorbs radiation across the full spectrum of UVA (ultraviolet light in the range of 320-400nm). The major drawback is its rapid degradation on UV exposure, thus, it is usually combined with other photostable agents to maintain its protective effect for a longer time period. Avobenzone has low allergenicity, though added photostabilsers may increase skin irritation. It is oil soluble and some of the ingredient applied topically is absorbed into circulation. The implications of this absorption, if any, are not yet known.

Beeswax

Beeswax - a wax ester secreted by honeybees. Beeswax is an occlusive which provides a barrier to water loss through the outer layer of skin. Beeswax also supplies moisture and has emulsifying (blending) properties.

Butylene glycol - a transparent liquid which acts as a solvent to decrease viscosity and aids the absorption of other ingredients in the formulation deeper into the skin. As a humectant, Butylene glcol is an efficient hydrator.

Caprylic/capric triglyderide (fractionated coconut oil) - a refined oil made from glycerin and coconut oil. Caprylic triglyceride is odourless, colourless and rapidly penetrates the skin. It functions as an occlusive, to minimise dehydration by barrier mechanism, and as an emollient, to smooth skin and reduce flakiness. Caprylic triglyceride is also sometimes used to thicken product or promote dispersal of other ingredients.

Cyclomethicone - a type of silicone which functions as an emollient. Cyclomethicone provides lubrication or “skin slip” and imparts a silky feel to skin. Similar to dimethicone, it is water-proof and noncomedogenic, though has a drier consistency.

Tumeric roots from which curcumin is derived

Curcumin - a yellow coloured botanical (polyphenol) obtained from the root of turmeric. Occasionally used to provide a natural yellow colouring, more often though tetrahydrocurcumin (a form of curcumin with hydrogen molecules added) is used because it is off-white, a more desirable colour for skin care formulations. While both are potent skin antioxidants, tetrahydrocurcumin also prevents the lipids used in moisturisers from degrading.

Dimethicone - the second most common ingredient in skin care products, dimethicone is a major component of oil-free moisturisers and foundations. While also hypoallergenic, nonacnegenic and noncomedogenic, dimethicone is often combined with petrolatum to impart a lighter, silkier texture. Dimethicone is an occlusive and reduces water loss by causing the skin cells to contract closer together, but is permeable to water vapour, allowing for perspiration to evaporate. It also has some additional action as an emollient, smoothing the skin. Dimethicone confers properties of water resistance to the product, thus it does not blend with sebum (oily secretion naturally present in skin).

Ecamsule (Mexoryl SX or terephthalylidene dicamphor sulfonic acid) - the newest chemical sunscreen filter, ecamsule is acidic and water-soluble. It absorbs radiation across the entire UVA spectrum and part of the UVB (peak absorption at 345 nm). It is photostable, meaning it does not degrade and lose effectivemess upon UV exposure. Ecamsule is minimally absorbed into the skin and rarely causes irritation.

Gelatin - a protein derived from the bones, skin and connective tissue of animals. Gelatin is most commonly used in skin care formulations as a thickening agent. It also has water-binding properties, making it a good humectant.

Glycerin (glycerol or glycerine) - found in many moisturisers, glycerin acts is an effective humectant. It alters the water balance in skin by influencing ‘aquaporins’, the channels used to transport water into and out of the cell. When combined with an occlusive to stop evaporation, it is able to quickly rehydrate the skin’s surface. The affect of glycerin is able to continue after the product has disappeared, this is known as a reservoir effect. Some combination of glycerin, petrolatum and dimethicone generally forms the basis of most skin care products, with other ingredients added to create a particular desired effect.

Glyceryl stearate - a white or ivory, waxy fat which serves as a common emollient and surface lubricant in skin-care products. It has some emulsifying (blending) properties and forms an occlusive layer on the skin which acts as a barrier to slow water loss. Glyceryl stearate may also promote resistance to freezing and formation of dry crusts in the product it is added to. It minimises the greasy finish of oils added to the mixture and is often used as a thickening agent.

Green tea (Camellia sinensis) - a botanical extract from leaves of the green tea plant that has been used in Chinese medicine for thousands of years. The tea contains polyphenols which act as powerful antioxidants to fight the symptoms of skin aging. When applied topically green tea has anti-inflammatory properties, it also minimises erythema and edema (swelling caused by the accumulation of excess fluid) induced by UV radiation. Application of green tea polyphenols prior to UV exposure helps to reduce the formation of CPD photoproducts; lesions within the DNA of skin cells thought to contribute to the development of skin cancer.

Hyaluronic acid - naturally present in skin cells, hyaluronic acid attracts water into the corneocytes to condition the exterior layer of skin. It is purified as a white powder and is often used to increase the viscosity of aqueous (water-based) solutions. Hyaluronic acid may also help active ingredients in a product penetrate the skin.

Isopropyl palmitate - a colourless, liquid derived from palm or coconut oil. Isopropyl palmitate is an emollient which enhances the appearance of skin by restoring flexibility and suppleness. It is also used as a thickening agent in some preparations and may be comedogenic in some individuals. This liquid can function as an opacifier (turns a mixture opaque) in gels or creams and as binder to combine powdered ingredients to form cakes.

Lanolin - A water-insoluble wax mainly derived from sheep’s wool. Lanolin, along with mineral oil, is the second most effective occlusive, reducing water loss through the skin by 20-30%. It is broadly used in skin care products and has some additional emollient and emulsifying properties. Lanolin may cause allergic reaction in individuals with sensitive skin.

Menthyl anthranilate (meradimate) - a synthetic sunscreen agent (filter) which acts to absorb UV radiation in the UVA spectrum up to 336nm. Due to its high stability under sunlight, menthyl anthranilate is often used to stop the deterioration of a product. It rarely induces allergic reaction.

Mineral oil (liquid paraffin) - a colourless, odourless and tasteless oil purified from petroleum. Mineral oil is a widely used occlusive as it is inexpensive and, along with petrolatum, is one of the most nonirritating moisturising skin care ingredients available. It is the main component of baby oil and has many applications such as make-up removal and relief of mild eczema and inflammation. Contrary to popular belief, cosmetic grade mineral oil is not comedogenic (pore-blocking).

Oxybenzone (Benzophenone-3) - an organic sunscreen filter which is water-insoluble and a powder at room temperature. A relatively weak UV absorber, oxybenzone covers the UVB spectrum and part of the UVA spectrum (below 330nm). Highly stable, it is often used to protect other sunscreen filters from UV degradation. Oxybenzone is usually added in low concentrations since it can be allergenic and tends to give the sunscreen a sticky texture.

Paraffin wax

Paraffin - a white hydrocarbon wax similar to mineral oil, derived from petroleum. Paraffin moisturises by creating an occlusive layer over the skin, it is also used as a product thickener. The main limitation of paraffin is that large amounts may be comedogenic.

Petrolatum (petroleum jelly or soft paraffin) - with the exception of water, petrolatum is the most common ingredient in skin care products and the most effective occlusive; decreasing water loss from the epidermis by over 98% when its concentration is greater than five percent. It diminishes grooves and creases by rehydrating the skin and may also slightly decrease itching and pain by covering nerve endings in the epidermis. Petrolatum penetrates the upper layer of the skin and aids in the production of lipids vital for barrier repair. Petrolatum is hypoallergenic, nonacnegenic and noncomedogenic (does not block skin pores). The main drawback of this ingredient is its waxy, greasy texture.

Panthenol (Pantothenic acid or vitamin B5) - derived from vitamin B5, panthenol works as a humectant to help hydrate the stratum corneum, assist with wound healing and reduce dry or scaly skin. A small number of studies suggest that pantothenic acid may be an effective treatment for acne vulgaris, though this is largely unsubstantiated.

Propylene glycol - a colourless, viscous alcohol, propylene glycol hydrates skin by occluding it, preventing excess water loss. It is commonly used as a vehicle for other the application of other ingredients such as vitamins and other active components. Propylene glycol is an effective humectant and stabilises cosmetic solutions. It also possesses the skin conditioning properties of an emollient, smoothing the skin and increasing pliability to impart a soft texture. In high concentrations, propylene glycol may be a skin sensitiser in susceptible individuals.

Tomatoes rich in retinol

Retinol (Vitamin A) - a botanical (a carotenoid) which can be found in fruits and vegetables with red, orange or yellow colouring. Retinol is the natural form of vitamin A and when applied topically it acts as an antioxidant. It has been reported to minimise the fine lines and wrinkles associated with photoaging and has a low irritative potential.

Silymarin - an extract of the milk thistle plant (Silybum marianum) which contains three botanicals (flavonoids) from the leaves, seeds and fruit. Silymarin is a strong antioxidant which neutralises reactive oxygen species, preventing damage to cells which can lead to premature skin aging.

Sodium lactate - a salt of lactic acid similar to ammonium lactate. Sodium lactate acts mainly as a humectant, to bind water and moisturise the skin. It also has the properties of an exfoliant and a buffering agent.

Sorbitol - a sugar-based alcohol found naturally in berries, apples and seaweed; it can also be synthetically manufactured. Sorbitol is a humectant which conditions the skin to reduce dryness and flaking. It also acts as a thickening agent for cosmetic solutions and an emollient to smooth and soften the outer layer of skin.

Soy derived from soy beans

Soy - derived from soybeans, soy contains an abundance of the botanicals known as flavonoids. As well as acting as effective antioxidants, research suggests that some of these flavonoids may add volume to skin and stimulate the production of collagen to improve the appearance of damaged or aging skin.

Sulisobenzone (Benzophenone-4) - similar to oxybenzone, sulisobenzone is a chemical UV filter which is a powder in its natural state. It is a fairly weak sunscreen which primarily absorbs wavelengths in the short UVA (UVA-2, 320-340 nm) range and also some UVB radiation. Inadequate for UV protection on its own, sulisobenzone is very chemically stable and thus commonly combined with other filters to prevent their inactivation by UV light. Benzophenones are easily absorbed by the skin, though the health implications of this are still unclear. Sulisobenzone is a potential allergen, with one 2007 study finding it to be the organic filter most likely to induce contact dermatitis.

Titanium dioxide - a sunscreen filter which creates a physical barrier to the entire spectrum of UV radiation as well as certain wavelengths of visible light. To date, zinc and titanium oxide are the only inorganic filters approved for use in the U.S. In the past, preparations with these ingredients often left a white film on the skin surface. Recent innovation has allowed the development of smaller, nanoparticles which improved this cosmetic quality. Both may cause skin whitening in high concentrations and, as a result, are usually combined with organic filters.

Urea - synthetic urea, used cosmetically, is in the form of white or clear crystallised powder. Urea is a natural component of skin tissue which, as with other humectants, increases the water content of the top layers of skin. It can also function as a buffering agent and exfoliant; large concentrations may cause skin irritation.

Zinc oxide - similar to titanium dioxide, zinc oxide is an inorganic sunscreen filter which functions to physically block both UVA and UVB rays, as well as some visible light, from penetrating the skin. As with its counterpart, it comes in the form of a powder and may cause skin whitening in high concentrations.

Kawada, A et al., 2009, ‘Evaluation of anti-wrinkle effects of a novel cosmetic containing retinol using the guideline of the Japan Cosmetic Industry Association’, The Journal of Dermatology, 36:583-586.

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